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Viruses 2019, 11(2), 148; https://doi.org/10.3390/v11020148

Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions

1
Division of Infectious Diseases, Ospedale San Raffaele, 20132 Milan, Italy
2
Vita-Salute University, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
Received: 28 December 2018 / Revised: 5 February 2019 / Accepted: 7 February 2019 / Published: 11 February 2019
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Abstract

Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs that confer resistance to NS5A inhibitors. Methods: From a publicly accessible database, we retrieved 58 complete GT-3 genomes and an additional 731 worldwide NS5A sequences from patients infected with GT-3 that were naive to direct-acting antiviral treatment. Results: We performed a phylogenetic analysis of NS5A domains in complete HCV genomes to determine more precisely HCV-GT-3 subtypes, based on commonly used target regions (e.g., 5′untranslated region and NS5B partial domain). Among 789 NS5A sequences, GT-3nonA subtypes were more prevalent in Asia than in other geographic regions (p < 0.0001). The A30K RAS was detected more frequently in HCV GT-3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. Conclusions: These results provided information on the accuracy of HCV-3 subtyping with a phylogenetic analysis of the NS5A domain with data from the Los Alamos HCV genome database. This information and the worldwide geographic distribution of RASs according to HCV GT-3 subtypes are crucial steps in meeting the challenges of treating HCV GT-3. View Full-Text
Keywords: NS5A replication complex inhibitors; resistance-associated substitutions (RASs); HCV genotype 3 subtypes; geographic distribution; natural polymorphisms NS5A replication complex inhibitors; resistance-associated substitutions (RASs); HCV genotype 3 subtypes; geographic distribution; natural polymorphisms
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Bagaglio, S.; Messina, E.; Hasson, H.; Galli, A.; Uberti-Foppa, C.; Morsica, G. Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions. Viruses 2019, 11, 148.

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